Charcot-Leyden Crystal (CLC)protein, which forms the distinctive bipyramidal crystals seen as a hallmark of eosinophil participation in inflammatory reactions, was originally identified as eosinophil lysophospholipase (LPLase). However, we have shown that CLC is not eosinophil LPLase, rather, it belongs to the galectin super family of animal lectins based on amino acid sequence, 3D protein structure, lack of LPLase activity, and as shown by others, gene structure; it is now designated as galectin-10. Our X-ray crystal structure showed CLC protein to be nearly identical to human galectin- 1, -2, -3 and -7, and to possess a carbohydrate recognition domain (CRD) capable of binding mannose, but not standard Beta-galactoside sugars generally recognized by galectins. We recently showed that one of the eosinophil?s LPLases is identical to the 75KD pancreatic LPLase, and CLC interacts with this LPLase and two other proteins that can also be recognized by anti-LPLase antibodies. Based on this finding, and our prior report that COS cells transfected with the cDNA encoding CLC protein exhibited higher LPLase activity than control cells, we propose to test the hypothesis that CLC protein interacts with LPLases and activates or stabilizes LPLase activity in human eosinophils. Specifically, we propose: (1) to define structure-function relationships for CLC protein?s carbohydrate-binding activities, (2) to identify biologically relevant ligands for CLC protein - the 75KD "pancreatic" LPLase and others, (3) to characterize the mechanisms of interaction of CLC protein with the 75 KD LPLase and other ligand(s), and (4) to study the functional intracellular interactions of CLC protein and LPLase(s about in vivo.